The interaction of short and ultrashort pulsed laser radiation with living systems is not well understood and is an important area of investigation in laser medicine and biology. The objective of our research program is to obtain new information on the biological response and photophysics of short and ultrashort pulsed laser tissue interactions through the application of state of the art laser generation and measurement techniques. We propose to (1) investigate laser tissue interaction in the femtosecond regime by studying primate retinal injury thresholds and damage mechanisms produced by exposure to high intensity femtosecond single laser pulses as well as low energy, high repetition rate pulse trains. Damage thresholds will be determined and fluorescein angiography and ultrastructural studies performed on selected lesions. The high field intensities but low energies of the femtosecond laser exposures is expected to produce nonlinear photochemical damage with minimal thermal effects resulting in a damage mechanism and tissue response distinct from that produced by longer pulse durations. (2) The use of nanosecond and picosecond laser pulses to produce optical breakdown and produce clinically useful effects from acoustic transients has recently become an important therapeutic technique. We will investigate the transient properties of laser induced breakdown using a variety of measurement techniques developed in picosecond time resolved spectroscopy. In particular, pump and probe measurements will be applied to study the initiation, evolution, and propagation of plasma absorption, acoustic transients, and liquid-gas phase changes which are associated with laser induced breakdown.